title: Genetics and epigenetics of the X chromosome.
abstract: A consequence of Mendelian inheritance of X-linked traits is that women are more than equal to men in the face of X-linked diseases, protected as they are by the presence of two X chromosomes in their genome. This potentially beneficial inequality is diminished by the molecular mechanism known as X-chromosome inactivation (XCI), which triggers the transcriptional silencing of one of the X chromosomes in each female cell. The determination of which X to inactivate, a process that occurs during early embryogenesis, is random and clonally inherited. As a result, females are mosaic for the expression of X-linked genes. XCI is a highly regulated process involving large noncoding RNAs, chromatin remodeling, and nuclear reorganization of the X chromosome. It is a paradigm for epigenetic regulation and is frequently used as a biomarker for monitoring long-range gene reprogramming during cell differentiation and dedifferentiation. Our review analyses how XCI affects the expression of X-linked mutations, describes some of the most recent discoveries on the molecular mechanisms triggering XCI, and explores the therapeutic potentialities of the XCI process per se.
authors.affiliation: Département de Biologie du Développement, Unité de Génétique Moléculaire Murine, Institut Pasteur, CNRS, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Morey
authors.forename: Philip
authors.initials: P
authors.lastname: Avner
mesh_terms: D000818:Animals; D041321:Chromosomes, Human, X / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D006801:Humans; D008297:Male; D012727:Sex Characteristics; D012729:Sex Chromosome Aberrations; D014960:X Chromosome / Q000235:genetics*; D049951:X Chromosome Inactivation / Q000235:genetics*